Best Pract Res Clin Endocrinol Metab 2018 Apr 31;32(2):141-154. Epub 2018 Jan 31.
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. Electronic address:
Metabolic disorders deriving from the non-responsiveness of target organs to hormones, which manifest clinically similar to the deficiency of a given hormone itself, derive from molecular alterations affecting specific hormone receptors. Pseudohypoparathyroidism (PHP) and related disorders exemplify an unusual form of hormone resistance as the underlying molecular defect is a partial deficiency of the α subunit of the stimulatory G protein (Gsα), a key regulator of cAMP signaling pathway, or, as more recently described, of downstream effector proteins of the same pathway, such as PKA regulatory subunit 1A (R1A) and phosphodyestarase type 4D (PDE4D). In this group of diseases, resistance to hormones such as PTH, TSH, gonadotropins and GHRH may be variably present, so that the clinical and molecular overlap among these different but related disorders represents a challenge for endocrinologists as to differential diagnosis and genetic counseling. Read More